Long Noncoding RNA NEAT1 Promotes the Progression of Breast Cancer by Regulating miR-138-5p/ ZFX Axis

Abstract

Background: Growing evidence demonstrated that long noncoding RNAs (lncRNAs) were involved in the progression of diverse cancers, including breast cancer (BC). Recent studies indicated that lncRNA nuclear enriched abundant transcript 1 (NEAT1) was overexpressed and facilitated tumor processes in many cancers. Nevertheless, the underlying mechanism of NEAT1 in regulating BC progression is still largely unknown. Materials and Methods: The abundance of NEAT1, microRNA-138-5p (miR-138-5p), and zinc finger protein X-linked (ZFX) was assessed by quantitative real-time polymerase chain reaction. Cell Counting Kit-8 (CCK-8) assay, flow cytometry, and transwell assay were utilized to evaluate cell proliferation, apoptosis, migration, and invasion, respectively. Western blot analysis was applied to detect the protein expression of CyclinD1, Bax, E-cadherin, and ZFX. The interaction between miR-138-5p and NEAT1 or ZFX was predicted by starBase v3.0 and validated by dual-luciferase reporter, RNA pull-down, and RNA immunoprecipitation assays. The mice xenograft model was established to investigate the roles of NEAT1 in vivo. Results: NEAT1 was highly expressed and miR-138-5p was lowly expressed in BC tissues and cells. NEAT1 interference or miR-138-5p restoration repressed cell proliferation, migration, and invasion but accelerated apoptosis in BC cells. Moreover, miR-138-5p directly interacted with NEAT1 and its knockdown reversed the suppressive impact of NEAT1 downregulation on the progression of BC cells. In addition, ZFX was a downstream target of miR-138-5p and its upregulation attenuated the antitumor role of miR-138-5p in BC cells. Besides, ZFX expression was positively regulated by NEAT1 and inversely modulated by miR-138-5p. Furthermore, interference of NEAT1 inhibited tumor growth by upregulating miR-138-5p and downregulating ZFX. Conclusion: NEAT1 affected BC progression through modulating miR-138-5p/ZFX axis, providing a vital theoretical basis for BC treatment.

Keywords: NEAT1; ZFX; breast cancer; miR-138-5p.